Activation and function of receptor tyrosine kinases in human clear cell renal cell carcinomas
文献类型：期刊论文
| 作者 | Zhang, Qing2 ; Liu, Jian-He1; Liu, Jing-Li2; Qi, Chun-Ting2; Yan, Lei2; Chen, Yu2; Yu, Qiang2
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| 刊名 | BMC CANCER
 |
| 出版日期 | 2019-11-05 |
| 卷号 | 19期号:1页码:13 |
| 关键词 | Receptor tyrosine kinases (RTKs) Activation and function Clear cell renal cell carcinomas (ccRCCs) Targeted therapy PDGFR beta Stroma cells |
| DOI | 10.1186/s12885-019-6159-2 |
| 通讯作者 | Yu, Qiang(qyu@sibs.ac.cn) |
| 英文摘要 | Background The receptor tyrosine kinases (RTKs) play critical roles in the development of cancers. Clear cell renal cell carcinoma (ccRCC) accounts for 75% of the RCC. The previous studies on the RTKs in ccRCCs mainly focused on their gene expressions. The activation and function of the RTKs in ccRCC have not been fully investigated. Methods In the present study, we analyzed the phosphorylation patterns of RTKs in human ccRCC patient samples, human ccRCC and papillary RCC cell lines, and other kidney tumor samples using human phospho-RTK arrays. We further established ccRCC patient-derived xenograft models in nude mice and assessed the effects of RTKIs (RTK Inhibitors) on the growth of these cancer cells. Immunofluorescence staining was used to detect the localization of keratin, vimentin and PDGFR beta in ccRCCs. Results We found that the RTK phosphorylation patterns of the ccRCC samples were all very similar, but different from that of the cell lines, other kidney tumor samples, as well as the adjacent normal tissues. 9 RTKs, EGFR1-3, Insulin R, PDGFR beta, VEGFR1, VEGFR2, HGFR and M-CSFR were found to be phosphorylated in the ccRCC samples. The adjacent normal tissues, on the other hand, had predominantly only two of the 4 EGFR family members, EGFR and ErbB4, phosphorylated. What's more, the RTK phosphorylation pattern of the xenograft, however, was different from that of the primary tissue samples. Treatment of the xenograft nude mice with corresponding RTK inhibitors effectively inhibited the Erk1/2 signaling pathway as well as the growth of the tumors. In addition, histological staining of the cancer samples revealed that most of the PDGFR beta expressing cells were localized in the vimentin-positive periepithelial stroma. Conclusions Overall, we have identified a set of RTKs that are characteristically phosphorylated in ccRCCs. The phosphorylation of RTKs in ccRCCs were determined by the growing environments. These phosphorylated/activated RTKs will guide targeting drugs development of more effective therapies in ccRCCs. The synergistical inhibition of RTKIs combination on the ccRCC suggest a novel strategy to use a combination of RTKIs to treat ccRCCs. |
| WOS关键词 | GROWTH-FACTOR ; CSF RECEPTOR ; CANCER ; EXPRESSION ; INSULIN ; MECHANISMS ; BIOLOGY ; MET ; VHL |
| 资助项目 | China National Key Research and Development Program[2018YFC1705505] ; National Natural Science Foundation of China[81673465] |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000494804200001 |
| 出版者 | BMC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/281824]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Yu, Qiang |
| 作者单位 | 1.Shanghai Jiao Tong Univ, Xin Hua Hosp, Dept Urol, Sch Med, 1665 Kongjiang Rd, Shanghai, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, 555 Zuchongzhi Rd,Room 2-224, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Qing,Liu, Jian-He,Liu, Jing-Li,et al. Activation and function of receptor tyrosine kinases in human clear cell renal cell carcinomas[J]. BMC CANCER,2019,19(1):13. |
| APA | Zhang, Qing.,Liu, Jian-He.,Liu, Jing-Li.,Qi, Chun-Ting.,Yan, Lei.,...&Yu, Qiang.(2019).Activation and function of receptor tyrosine kinases in human clear cell renal cell carcinomas.BMC CANCER,19(1),13. |
| MLA | Zhang, Qing,et al."Activation and function of receptor tyrosine kinases in human clear cell renal cell carcinomas".BMC CANCER 19.1(2019):13. |
入库方式： OAI收割
来源：上海药物研究所
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